Episodes Of Neutropenia Research Articles

Risk of Neutropenia in Adults Treated with Piperacillin-Tazobactam or Cefazolin: A Retrospective Cohort Study.

Neutropenia is an adverse effect associated with the use of several antibiotics, including piperacillin-tazobactam (P/T). Previous findings have suggested that the risk of neutropenia in children is significantly higher with P/T than with ticarcillin-clavulanate. To compare the risk of neutropenia associated with P/T and with cefazolin in an adult population and to describe the characteristics of neutropenia episodes observed. This descriptive retrospective study involved patients aged 18 years or older who received a minimum of 10 days of treatment with P/T or cefazolin between January 2009 and December 2013. Patients who experienced neutropenia (absolute neutrophil count < 1.5 × 109/L) were compared, using univariate and multivariate logistic regression models, between those who received P/T and those who received cefazolin. A total of 207 patients were included (104 who received P/T and 103 who received cefazolin). Ten episodes of neutropenia were observed, 5 with each antibiotic (4.8% and 4.9%, respectively; odds ratio 0.99, 95% confidence interval 0.278-3.527). The mean cumulative dose of piperacillin was 290.4 g among patients who experienced neutropenia and 247.0 g among all patients treated with P/T, and the mean treatment duration was 24.0 days and 21.0 days, respectively. The average time before the onset of neutropenia was slightly longer with P/T than with cefazolin (22.0 versus 17.2 days, p = 0.38). Although these results require confirmation in a larger clinical trial (to lessen possible attribution bias), the risk of neutropenia appeared to be similar between P/T and cefazolin.

Safety and risk of febrile recurrence after early antibiotic discontinuation in high-risk neutropenic patients with haematological malignancies: a multicentre observational study.

Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies. A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence. Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), P = 0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), P = 0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), P = 0.07] and 30 day mortality [1.4% (2/147) versus 2.7% (4/150), P = 0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), P < 0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P < 0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence [HR = 2.31 (95% CI = 1.4-3.8), P < 0.001] and stage III-IV oral mucositis with bacteraemia [HR = 2.26 (95% CI = 1.22-4.2), P = 0.01]. After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.

Efficacy and Safety of Piperacillin-Tazobactam and Cefepime as Empirical Therapy for Febrile Neutropenic Children with Acute Lymphoblastic Leukaemia (ALL)

Background: Infection is a major clinical challenge in ALL treatment. Prompt administration of empirical antibiotic in febrile neutropenic patients has reduced the mortality. Both Cefepime or Piperacillin-Tazobactam has been used as empirical treatment.&#x0D; Objective: To compare the efficacy and safety between Piperacillin-Tazobactam with Cefepime in febrile neutropenic children with ALL.&#x0D; Materials and methods: This randomized study was conducted from August 2015 to August 2016 in BSMMU. Sixty one episodes of febrile neutropenia in children with ALL, aged 0 to18 years were included in this study. Patients were randomized into two groups. One group received Piperacilln/Tazobactam and another group received Cefepime and data of 60 febrile neutropenic episodes were analyzed.&#x0D; Results: Febrile neutropenic episodes in the Piperacillin/Tazobactam group were 28 and in Cefepime group was 32 episodes and 34(57.63%) were male and 25 (42.37%) female. Median age was 5 years and 38(62.3%) neutropenic episodes were in induction phase. Majority had fever without focus 21(35%). Microorganisms isolated in 13 (21.66%) patients and majority 6 (46.15%) had blood infection. Most of the isolated organisms were Gram negative 11(84.61%). Overall treatment success without modification in the Piperacillin/Tazobactam group was 17(60.7%) and in Cefepime group 18 (56.3%) and that comparison was not statistically significant (p= 0.732). Significant difference was also not found comparing the mean duration of fever, neutropenia and hospital stay.&#x0D; Conclusion: Both Piperacillin/Tazobactam and Cefepime were found effective and safe as an empirical therapy for febrile neutropenic children with ALL.&#x0D; BANGLADESH J CHILD HEALTH 2021; VOL 45 (2) : 83-88

Chemotherapy Induced Neutropenic Fever and Its Response to Empirical Antimicrobial Therapy

Objective: To find out the frequency of chemotherapy-induced febrile neutropenia (FN) in children diagnosed with Acute Lymphoblastic Leukemia (ALL) and its response to empirical antibiotic therapy.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Department of Peadiatric Oncology, Combined Military Hospital, Rawalpindi Pakistan, from Nov 2017 to Oct 2018.&#x0D; Methodology: Newly diagnosed pediatric patients suffering from acute lymphoblastic leukemia between 1 to 15 years of age were included. All patients were treated with chemotherapy according to the United Kingdom National Randomized Trial for Children and Young adults with Acute Lymphoblastic Leukemia (UKALL) 2011 protocol. Patients with febrile neutropenic (FN) episodes were treated with empirical antimicrobial therapy as per hospital guidelines. Patients ‘response to antimicrobial therapy, blood culture results and related complications were noted.&#x0D; Results: Out of a total 77 patients, 45 (58.4%) had 69 episodes of febrile neutropenia (FN), 62 (78.5%) episodes of febrile neutropenia (FN) were started empirical treatment with first-line antibiotics (piperacillin-tazobactam and amikacin) whereas 15 (21.7%) episodes of febrile neutropenia (FN) not responding to the 1st line were shifted to second-line antibiotics (meropenem and amikacin). Mean duration of fever was 4.1 ± 2.8 days on 1st line antibiotic regimen, 2.6 ± 1 days on 2nd line antibiotics and 6.3 ± 3.3 days on combination with antifungal drug. Ten patients received antifungal therapy empirically. Efficacy of the 1st line and the 2nd line was 72.5% and 77% respectively. Staphylococcus aureus was the most frequent organism isolated from blood culture results. During the induction phase, 10 (12.9%) patients..............

Polatuzumab vedotin with dose-adjusted etoposide, cyclophosphamide, doxorubicin, and rituximab (Pola-DA-EPCH-R) for upfront treatment of aggressive B-cell non-Hodgkin lymphomas.

7546 Background: The phase 3 POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the R-CHOP regimen for large B-cell lymphomas. However, it is unknown if Pola can be safely incorporated into intensified regimens typically utilized for the highest risk histologies. To address this question, we conducted a prospective trial (NCT04231877) evaluating Pola with dose adjusted etoposide, cyclophosphamide, doxorubicin, and rituximab (Pola-DA-EPCH-R). Methods: This is a single center, open label, investigator-initiated clinical trial of 6 cycles of Pola-DA-EPCH-R in aggressive large B-cell lymphomas where DA-EPOCH-R is considered standard (eg. HGBCL, PMBCL, and select DLBCL-NOS). Pola is given at 1.8 mg/kg on day 1 without intra-patient dose escalation. All other components of the regimen including escalation of chemotherapy dosing based on neutrophil and platelet nadirs from the previous cycle are given according to Dunleavy et al NEJM 2013. The primary objective is to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with pre-specified suspension rules if the lower limit of an 80% confidence interval cannot exclude a DLT rate of &gt; 20%. Efficacy, survival, and correlative analyses will also be performed. Results: 18 patients enrolled on study and as of Feb 15, 2022, 3 patients remain on study treatment. Median age was 64 years (range 41-74). With only 3 DLTs, the study met its primary endpoint for safety. Five SAEs were observed, including one grade 5 sepsis/typhlitis (during cycle 1), 3 episodes of febrile neutropenia, and a grade 3 perforation of a colonic diverticula which required a treatment delay of 12 days before completing all expected study therapy. Other grade 3+ non-heme AEs in more than one pt. include hyperglycemia (17%), oral mucositis (17%), incidental asymptomatic pulmonary embolism (17%), abdominal pain (11%), and hypokalemia (11%). Grade 1 peripheral sensory neuropathy was uncommon (22%), no grade 2+ neuropathy was observed. One patient required a decrease in Pola dosing due to a platelet nadir at dose level 1. Among those with at least 2 cycles of treatment, 94% were able to increase chemotherapy to at least dose level 2 (Table). Post cycle 2 interim overall response rate (ORR) and complete response (CR) rate was 88% and 24%, respectively. EOT ORR and CR was 93% and 71%, respectively, with one PD. Updated data will be presented at the meeting. Conclusions: Using Pola at 1.8 mg/kg to replace vincristine in the DA-EPOCH-R regimen appears feasible and met its primary safety endpoint. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. Clinical trial information: NCT04231877. [Table: see text]

A phase II study of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma.

8012 Background: Daratumumab (dara), carfilzomib (K), pomalidomide (P), and dexamethasone (d) are established in relapsed multiple myeloma (MM) with activity in 3-drug combinations including: dara Kd; dara Pd; and KPd. The paradigm in relapsed/refractory disease is moving towards more intensive and well-tolerated combinations to achieve deeper and more durable responses while ensuring tolerability. Quadruplet regimens are now becoming standard in newly diagnosed MM, and we explored a 4-drug regimen in relapsed disease. Preliminary results of a phase 2 study of dara KPd with a twice/week schedule of K showed an ORR of 86% in pts with a median of 1 prior line (Jasielec et al., ASH 2020). Here we report an ongoing study of dara with weekly KPd (dara wKPd) to improve the accessibility of this regimen. Methods: This phase 2 study (NCT04176718) will enroll up to 43 pts with relapsed/refractory MM who have received at least 1 prior therapy, including both lenalidomide and a proteasome inhibitor. Prior therapy with dara, K, or P was permitted except for K and P given together as last line of therapy. Dara wKPd was given on a 28-day schedule. Dara was given according to the dara Pd schedule. An initial cohort received dara 16 mg/kg iv (with first dose split over two days); the trial was amended to dara 1800 mg sc. K 56 mg/m2 iv was given weekly on days 1, 8, 15; for C1D1, dose was 20 mg/m2. P 4 mg was given po on days 1-21. Dex 40 mg was given weekly with the dose split over two days. Treatment was until progression or unacceptable toxicity. The primary endpoints are overall response and the safety profile of dara wKPd. Secondary endpoints include PFS. Results: At time of data cutoff, 24 pts were enrolled; median age was 65 (range 42-73), and median number of prior regimens was 2 (range 1-3). All pts were refractory to their last line of therapy and had prior lenalidomide and bortezomib. Additional prior therapies included: pomalidomide (54%), carfilzomib (13%), ixazomib (46%), cyclophosphamide (4%), auto SCT (29%). High risk FISH was present (out of 24 pts): del 17p (13%); t(14;16) (8%); gain of 1q (46%). Median follow up was 8.4 months. 2 pts came off study due to neutropenia leading to delay in treatment. Grade 3-4 hematologic AEs included neutropenia (46%) and thrombocytopenia (25%). There was 1 episode of febrile neutropenia. Common non hematologic AEs (all; grade 3-4) included fatigue (42%; 0%); dyspnea (38%; 4%); increase in ALT/AST (29%; 8%); insomnia (21%; 0%); neuropathy (17%; 0%). 22 pts were evaluable for response, with an overall response rate of 95% (PR 23%, VPGR 68%, CR 5%). Median PFS at 12 months was 86.2% (95% CI, 70%-100%). Conclusions: Dara wKPd shows some of the highest response rates (95%) reported to date in relapsed/refractory MM. This likely reflects the incorporation of 4 active drugs in 1 regimen and builds on the efficacy of dara-based triplet regimens, with manageable toxicity and convenience of weekly K. Clinical trial information: NCT04176718.

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study.

Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. A total of 346 children (age, 9.8 years; IQR, 6.6-13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3-7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P<0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01 to 0.18; P<0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years; P=0.05), age at first rituximab treatment (8.0 versus 10.0 years; P=0.01), and history of steroid resistance (28% versus 18%; P=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%; P=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.

The impact of COVID-19 lockdown measures on rates of febrile neutropenia in a cohort of Irish patients receiving chemotherapy.

e18784 Background: Febrile neutropenia in patients receiving chemotherapy is a life-threatening condition requiring prompt attention. This condition may also result in dose reductions, delays, or discontinuations of chemotherapy which compromise patient outcomes. This study seeks to evaluate the impact of COVID19 “lockdown” public health measures in Ireland on the incidence of febrile neutropenia in patients who were receiving cytotoxic chemotherapy regimens. Methods: All patients receiving chemotherapy at the Bon Secours Hospital Cork who were admitted with neutropenia and fever during two separate time periods were included in the study: 1st April 2018 to 31st March 2019 (“pre-pandemic year”) and 1st April 2020 to 31st March 2021 (“pandemic year”). The pandemic year selected equates to a period of heightened infection control measures in Irish society, featuring public health advice re social distancing, routine mask wearing in public and successive lockdown waves. Retrospective chart review was performed on all patients admitted to the oncology inpatient ward who had blood cultures on admission to determine the number of these patients who were neutropenic at the time of blood culture draw. Similarly, pharmacy records were accessed to determine the number of unique chemotherapy items dispensed in each year in order to establish a rate of febrile neutropenia episodes per 100 chemotherapy items dispensed for each period. The incident rate ratio was calculated using the Exact Poisson Test. Results: During the pre-pandemic year there were 57 individual admissions with febrile neutropenia compared with 32 admissions during the pandemic year. There were 4581 chemotherapy units dispensed during the pre-pandemic year compared to 4628 during the pandemic year. The rate of febrile neutropenia episodes per 100 chemotherapy units dispensed was 1.24 (95% CI 0.94, 1.61) in the pre-pandemic year and 0.69 (95% CI 0.47, 0.98) in the pandemic year. The incident rate ratio is 1.80 (95% CI 1.14, 2.87, two-sided P = 0.007). 9 of 57 (16%) admissions in the pre-pandemic year were associated with positive blood cultures compared with 4 of 32 (13%) in the pandemic year (not significant by Fisher's exact test). Conclusions: Increased precautionary infection control measures during the COVID19 pandemic public health restrictions correlated with a significant reduction in the rate of febrile neutropenia amongst patients receiving cytotoxic chemotherapy. This suggests that there may be a role for similar measures for this patient cohort in the post-pandemic period. Options which patients may consider to employ include social distancing, wearing face-coverings and restricting social contacts while at risk of neutropenia from cytotoxic chemotherapy regimens.

Clozapine Rechallenge or Continuation Despite Neutropenia, an Extended Follow-up of a Consecutive Quebec Case Series.

Clozapine is the most efficacious antipsychotic for treatment-resistant schizophrenia. However, clozapine-induced neutropenia may warrant treatment discontinuation, hindering recovery. Several case reports describe clozapine rechallenge or continuation despite neutropenia, although many are subject to selective reporting, with incomplete information and short follow-up periods. Thus, consecutive case series, devoid of such bias, with long-term comprehensive follow-up are needed to better assess this practice. This study aimed to describe consecutively the evolution of every patient in the Québec City catchment area for whom clozapine was either reintroduced after neutropenia during a previous clozapine trial or was maintained despite a first neutropenia. Patients were identified through clozapine's national hematological monitoring database and their medical records between January 1, 2000, and October 22, 2017. Twenty-three patients were identified, 8 continued clozapine despite neutropenia, while 15 discontinued clozapine and attempted rechallenge; among the latter, 4 patients were successfully rechallenged after agranulocytosis without the use of granulocyte colony-stimulating factors, which is the largest published consecutively. A total of 6 patients experienced further neutropenia episodes. Every patient who had a neutropenia recurrence also had a possible explanation for neutropenia other than exposure to clozapine. After a median follow-up of 4.8 years, 16 patients were still on clozapine and 3 cases discontinued because of a hematological event. This study adds further data on the subject of clozapine rechallenge or continuation despite neutropenia. Clozapine rechallenge after agranulocytosis may be less perilous than first thought, but a systematic review on this specific subject is needed.

Microbiological profile and antibiotic susceptibility pattern in children with malignancy and febrile neutropenia

Neutropenia that occurs in hematologic malignancies or solid tumors may increase the risk of infection and lead to morbidity and mortality. This study aims to investigate the microbiological profile and antibiotic susceptibility pattern in children with malignancy and febrile neutropenia (FN). A cross-sectional study was conducted from January 2017 to June 2021 using medical records from the pediatric inpatient hematology-oncology ward of Dr. Soetomo General Hospital. The inclusion criteria are children with malignancy aged ≤ 18 years, experiencing a febrile episode of neutropenia, and were examined for blood culture at the onset of FN. A total of 291 children were eligible patients. Out of 291, 65 of them had a bacterial infection from blood cultures. Out of 65, almost 57% were dominated by Gram-negative bacteria (GNB). Gram-positive bacteria (GPB) that are often recognized are Staphylococcus hominis, Staphylococcus epidermidis, and Staphylococcus aureus. Meanwhile, the GNB are Pseudomonas aeruginosa and Klebsiella pneumoniae ESBL+. The majority of GNB is almost 100% resistant to ampicillin meanwhile, GPB also reported resistance to β-lactamase. We found no correlation between microorganism infection and malignancy. GNB and GPB are partially resistant to commonly used antibiotics, especially β-lactamases and ampicillin. Alternative therapies are needed to resolve this matter.

Risk Assessment of Neutropenia during Low-Dose Valganciclovir Prophylaxis for Heart Transplant Recipients.

The aim of this study was to investigate whether low-dose valganciclovir (VGCV) prophylaxis for cytomegalovirus (CMV) infection increased the risk of developing neutropenia in heart transplant recipients (HTRs). Forty-three HTRs receiving VGCV were divided into two groups: those who received VGCV prophylaxis (n = 22) and those who did not (n = 21). Neutropenia was defined as an absolute neutrophil count ˂1500/µL and was monitored for approximately one year post-transplantation. In the prophylaxis group, 77.3% (17/22) of HTRs experienced neutropenia, which was significantly higher than that in the no prophylaxis group (42.9% [9/21], p = 0.031). No significant differences in the duration of VGCV administration and cumulative dose up to the first neutropenia episode were observed between the groups. Meanwhile, the cumulative dose of mycophenolate mofetil was significantly higher in the prophylaxis group than in the no prophylaxis group (p = 0.018); the daily maintenance dose and regularly measured area under the concentration-time curve (AUC) of mycophenolic acid did not significantly differ between groups. In conclusion, the risk of developing neutropenia was higher in HTRs receiving low-dose VGCV prophylaxis than it was in those not receiving prophylaxis, probably not attributed to dosing period and cumulative dose of VGCV until the onset of neutropenia.

Real-world challenges in the management of acute myeloid leukemia: a single-center experience from North India.

The outcome of acute myeloid leukemia (AML) in low-middle-income countries (LMIC) is dismal due to delayed clinical presentation and infection-related complications. We aimed to analyze the outcome of patients with AML and the factors associated with its prognosis. A retrospective observational study was conducted at a tertiary care university hospital in North India from January 2015 to December 2019. A total of 137 AML patients (median age 32year (3-66years) received intensive chemotherapy during study period. The median delay from diagnosis to treatment was 45days (6-177days). Among the 352 febrile neutropenia (FN) episodes analyzed, 175 (49.7%) were culture positive; Gram-negative multi-drug resistant organism (MDRO) sepsis during induction being 57.4% with 34.5% infections due to carbapenem-resistant Enterobacteriaceae (CRE) leading to a mortality rate of 14.6%. The median EFS and OS were 12.0 ± 1.57 (95% CI 8.91-15.08) and 15.0 ± 2.44 (95% CI 10.21-19.78) months respectively. Multivariable analysis revealed significant difference in median OS between favorable vs high risk AML groups (20.0 (95% CI: 12.50-27.49) vs 9.0 (95% CI: 2.99-15.01) months; p = 0.002); time from diagnosis to treatment (< 30days vs ≥ 30days; not reached vs 9.0 (95% CI: 6.81-11.18) months; p = 0.001), performance status (1 vs 2 vs 3; not reached vs 12.0 (95% CI: 10.32-13.67) vs 4.0 (95% CI:2.77-5.22); p = 0.001), and attainment of complete remission vs induction failure (not reached vs 6.0 (95% CI: 3.78-8.21); p = 0.002). Patient-related factors like delayed treatment initiation and high incidence of MDRO-associated sepsis are critical determinants of AML outcome in LMIC.

Neutropenia and Infection Prophylaxis in Childhood Cancer.

Purpose of ReviewPediatric oncology patients frequently experience episodes of prolonged neutropenia which puts them at high risk for infection with significant morbidity and mortality. Here, we review the data on infection prophylaxis with a focus on both pharmacologic and ancillary interventions. This review does not include patients receiving hematopoietic stem cell transplantation.Recent FindingsPatients with hematologic malignancies are at highest risk for infection. Bacterial and fungal prophylaxis decrease the risk of infection in certain high-risk groups. Ancillary measures such as ethanol locks, chlorhexidine gluconate baths, GCSF, IVIG, and mandatory hospitalization do not have enough data to support routine use. There is limited data on risk of infection and role of prophylaxis in patients receiving immunotherapy and patients with solid tumors. Patients with Down syndrome and adolescent and young adult patients may benefit from additional supportive care measures and protocol modifications.SummaryConsider utilizing bacterial and fungal prophylaxis in patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. More research is needed to evaluate other supportive care measures and the role of prophylaxis in patients receiving immunotherapy.

Higher efficacy of oral etoposide for mobilization of peripheral blood stem cells in patients with multiple myeloma

Abstract This study compares the efficacy, toxicity, hematopoietic recovery, and cost of stem-cell mobilization using intermediate-dose cyclophosphamide (IDCy) plus granulocyte colony-stimulating factor (G-CSF) compared with etoposide (VP-16) plus pegylated granulocyte colony-stimulating factor (PEG-rhG-CSF) in multiple myeloma (MM) patients. Two hundred forty-four consecutive patients undergoing mobilization with IDCy (3-3.5 g/m 2 ) plus G-CSF (n = 155) were compared with patients receiving VP-16 plus PEG-rhG-CSF (n = 89), including oral etoposide (n = 65) and intravenous etoposide (n = 24). Compared with IDCy, VP-16 use was associated with significantly higher median peak peripheral blood CD34 + cell count (8.20 [range: 1.84-84] × 106/kg vs 4.58 [range: 0.1-27.9] × 106/kg, P = .000), and ideal CD34 + cell yield of more than 6 × 106/kg (56.8% vs 35.1%, P = .001), notably with a higher efficacy in oral VP-16 use compared with IDCy use (CD 34 + cell counts: median peak peripheral blood 5.87 vs 4.58 × 106/kg and ≥6 × 106/kg [48.4% vs 35.1%]). The median number of apheresis courses was reduced from two in the IDCy group to one in the VP-16 group (P = .000). IDCy use was associated with significantly more frequent episodes of neutropenia (70.2% vs 35.2%; P = .000), intravenous antibiotic use (13.2% vs 11.4%; P = .672), and hospitalization (P = .000). The recoveries of neutrophils and platelets after autologous stem-cell transplantation were significantly faster in the VP-16 group compared with the IDCy group (P = .000). Our data indicate robust stem-cell mobilization in MM patients with VP-16 delivered either orally or intravenously. When compared with intravenous VP-16, oral VP-16 mobilization was associated with significantly more convenient, lower average total costs, and especially decreased the risk of hospital visits and exposure.

Retrospective single-center experience with OEPA/COPDAC and PET-CT based strategy for pediatric Hodgkin lymphoma in a LMIC setting

ABVD regimen for Hodgkin lymphoma (HL) is frequently used in children and young adults in low-middle income countries (LMIC). The feasibility and safety data for ‘non-ABVD’ protocols from LMIC is limited. The retrospective study was conducted in a single center in India. The Euronet PHL-C1 based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following two OEPA cycles. Radiotherapy was administered for inadequate PET response. During the 10-year period, 143 patients with HL were treated. The mean age was 7.8 ± 2.5 years. Bulky disease was observed in 82 (59%). Treatment abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET response was observed in 41/119 (34.4%), of which 56.1% received radiotherapy. Twelve (29.3%) patients who were supposed to receive radiotherapy received 2-cycles of COPDAC instead. Sixty-nine episodes of febrile neutropenia were observed in 54 patients. Treatment-related mortality (TRM) was observed in 7 (5.3%). The majority of episodes of febrile neutropenia (61%) and TRM (86%) occurred in the first cycle of OEPA. The 4-year event-free survival (EFS) and overall survival (OS) were 86.2 ± 3.4% and 93.5 ± 2.2%, respectively. Nine (6.3%) patients relapsed. Bulky disease lacked association with inadequate PET response (p = .800) or relapse (p = 1.000). OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently in the first cycle of OEPA. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.

GMMA Technology for the Development of Safe Vaccines: Meta-Analysis of Individual Patient Data to Assess the Safety Profile of Shigella sonnei 1790GAHB Vaccine in Healthy Adults, with Special Focus on Neutropenia.

IntroductionShigellosis is a major health concern among children < 5 years of age from developing countries, and there are no widely available vaccines to prevent it. The GMMA-based 1790GAHB investigational vaccine against Shigella sonnei was well tolerated and immunogenic in phase 1 and 2 studies conducted in healthy adults from Shigella endemic and non-endemic populations. Based on pooled data of five individual trials, we assessed the association between vaccine administration and the risk of neutropenia as well as the overall safety profile of 1790GAHB.MethodsThe risk ratio (RR) of neutropenia was evaluated between participants receiving 1790GAHB (vaccinees) and active comparator/placebo (controls) using different ethnicity-specific absolute neutrophil count (ANC) thresholds established to define neutropenia. Safety was assessed in terms of solicited, unsolicited, and serious adverse events (AEs).ResultsOf the 279 participants, 11 (5.5%) vaccinees and 4 (5.0%) controls had ANC below the appropriate threshold within 7 days post-vaccination. RR was 0.96 [95% confidence interval (CI) 0.54–1.70]. When neutrophil counts of participants of African descent were measured against an ethnicity non-specific threshold, they resulted in neutropenia episodes in 30 (37.0%) vaccinees and 16 (30.2%) controls, while only 2 (2.5%) vaccinees and 1 (1.9%) control had neutropenia when the ethnicity-specific threshold was applied. RRs were 0.98 (95% CI 0.75–1.28) and 1.30 (95% CI 0.1–17.6), respectively. Solicited and unsolicited AEs were slightly more frequent among vaccinees than controls. No serious AEs, other than neutropenia cases, were recorded in the vaccine group.ConclusionBy applying the appropriate threshold, no increased risk of neutropenia was identified in vaccinees compared with the controls. The frequency of neutropenia events varied drastically when ethnicity-appropriate thresholds were applied. This observation highlights the importance of selecting appropriate cut-off values according to the correct population reference. Overall, the 1790GAHB vaccine demonstrated an acceptable safety profile.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00596-x.

Prospective cohort study of the predictive value of inflammatory biomarkers over clinical variables in children and young people with cancer presenting with fever and neutropenia.

Introduction Fever during chemotherapy induced neutropenia is a common and potentially life-threatening complication of the treatment of childhood cancer. Predictions of poor outcome could be enhanced by incorporating serum biomarkers of inflammation at presentation and reassessment. Methods A prospective cohort study was conducted of children under 18 years old, being treated for cancer or a cancer-like condition, who presented with fever (≥ 38.0°C) and neutropenia (neutrophil count < 0.5*10 9/L). Clinical features were recorded, along with three experimental inflammatory biomarkers: procalcitonin (PCT), interleukin-6 (IL-6) and interleukin-8 (IL-8). Outcomes included serious medical complications (SMC): any infection related mortality, critical care and organ support, severe sepsis, septic shock, significant microbiologically defined infection, or radiologically confirmed pneumonia. Results Biomarker assessments were undertaken in 43 episodes of fever and neutropenia, from 31 patients aged between four months and 17 years old (median six years): 20 were female and 22 had acute leukaemia. Five episodes of SMC were noted. PCT, IL-6 and IL-8 had poor individual discriminatory ability (C-statistic 0.48 to 0.60) and did not add to the value of clinical risk stratification tools. Insufficient data were collected to formally assess the value of repeated assessments. Conclusions Incorporating serum biomarkers of inflammation at presentation of episodes of fever with neutropenia in childhood does not clearly improve risk stratification. The value of serial assessments requires further investigation.

Cost-Effectiveness Analysis of PEG-rhG-CSF as Primary Prophylaxis to Chemotherapy-Induced Neutropenia in Women With Breast Cancer in China: Results Based on Real-World Data.

Background: Pegylated recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are more commonly and widely used than recombinant human granulocyte colony-stimulating factors (rhG-CSFs) in preventing chemotherapy-induced neutropenia in patients with stage II-IV breast cancer. To reduce the financial burden on these patients, the corresponding medical insurance directory needs to be revised. Objectives: To evaluate the cost-effectiveness of PEG-rhG-CSF versus rhG-CSF in patients with stage II-IV breast cancer in central China. Methods: Two Markov models, a chemotherapy model and a post-chemotherapy model, were developed to study the effects and costs, with a time horizon of 12 weeks and 35 years, respectively. Cost and probability input data were primarily obtained from a retrospective real-world study conducted in five tertiary hospitals. Propensity score matching was adopted to overcome retrospective bias. Other parameters were extracted from literature as well as advice from clinical experts. Univariate and probabilistic sensitivity analyses were conducted. Results: In the first chemotherapy model, PEG-rhG-CSF was associated with fewer episodes of febrile neutropenia (FN) (N = 19 per 1000 patients treated), infections (N = 24 per 1000 patients treated) and deaths (N = 2 per 1000 patients treated), but higher costs (¥36 more per patient treated). The post-chemotherapy model indicated that PEG-rhG-CSF led to higher gains in quality-adjusted life years (QALYs) (11.695 versus 11.516) in comparison to rhG-CSF. Sensitivity analysis showed that the cost of PEG-rhG-CSF had the greatest impact on the incremental costs, and incremental QALYs were very sensitive to the risk of RDI <85%. The probability of PEG-rhG-CSF being cost-effective compared to rhG-CSF was 66% at the willingness to pay (WTP) thresholds of ¥72,371 per QALY gained. Conclusion: According to this economic evaluation based on real-world data, PEG-rhG-CSF may be considered as a more cost-effective strategy relative to rhG-CSF for stage II-IV breast cancer patients in central China. However, to reflect a national perspective, further evidence is needed using data from larger-scale studies.

Survival outcomes associated with chemotherapy-induced neutropenia in the adjuvant treatment of colorectal cancer with FOLFOX.

81 Background: Patients undergoing adjuvant treatment with FOLFOX for colorectal cancer (CRC) are at risk of developing chemotherapy-induced neutropenia (CIN). We assessed survival outcomes in patients who develop CIN in this setting. Methods: We performed a retrospective chart review of patients with CRC treated with FOLFOX at our institution in Canada from 2013 to 2015. The survival follow-up cut-off date was August 2021. Demographic, treatment, and outcome data were collected. CIN was defined as ANC &lt;1.5, and all episodes of neutropenia were assumed to be the result of chemotherapy. Median OS was calculated using Kaplan-Meier product limit estimates. Results: A total of 302 patients were included (baseline demographics in the table). Median follow-up was 110 months. In the overall cohort, 174 patients (58%) had at least one episode of CIN. CIN occurred in 56% of those with stage II cancer, 43% of those with low risk stage III cancer (T1-3 and N1), and 45% of those with high risk stage III cancer (T4 or N2). Median time to first CIN event was 4.3 months. Among patients with at least one episode of CIN, the first CIN event occurred during the first 3 months of treatment in 110 (63%). Among patients with at least one episode of CIN, 79 (45%) received subsequent granulocyte colony-stimulating factor (GCSF). The median OS in the overall cohort was 171 months. For patients with and without CIN the median OS had not been reached, HR 0.84 (95% CI 0.55-1.29, p=0.43). The median OS for patients with CIN treated with and without GCSF had not been reached, HR 1.02 (95% CI 0.57-1.82, p=0.94). The 5-year survival rate for patients with and without CIN was 87% vs 77%. The 10-year survival rate for patients with and without CIN was 70% vs 64%. A trend toward improved survival in those with CIN remained when results were analyzed by cancer stage. Conclusions: Patients with CIN had a trend toward improved survival compared to those who did not have CIN. There was no indication that GCSF in the setting of CIN impacted survival. The causes for the potentially protective effect of CIN in the setting of adjuvant CRC treatment require further elucidation.[Table: see text]

Remote Monitoring of Patients With Hematologic Malignancies at High Risk of Febrile Neutropenia: Exploratory Study.

BackgroundFebrile neutropenia is one of the most common oncologic emergencies and is associated with significant, preventable morbidity and mortality. Most patients who experience a febrile neutropenia episode are hospitalized, resulting in significant economic cost.ObjectiveThis exploratory study implemented a remote monitoring system comprising a digital infrared thermometer and a pulse oximeter with the capability to notify providers in real time of abnormalities in vital signs that could suggest early clinical deterioration and thereby improve clinical outcomes.MethodsThe remote monitoring system was implemented and compared to standard-of-care vital signs monitoring in hospitalized patients with underlying hematologic malignancies complicated by a febrile neutropenia episode in order to assess the feasibility and validity of the system. Statistical analysis was performed using the intraclass correlation coefficient (ICC) to assess the consistency between the measurements taken using traditional methods and those taken with the remote monitoring system for each of the vital sign parameters (temperature, heart rate, and oxygen saturation). A linear mixed-effects model with a random subject effect was used to estimate the variance components. Bland-Altman plots were created for the parameters to further delineate the direction of any occurring bias.ResultsA total of 23 patients were enrolled in the study (mean age 56, SD 23-75 years; male patients: n=11, 47.8%). ICC analysis confirmed the high repeatability and accuracy of the heart rate assessment (ICC=0.856), acting as a supplement to remote temperature assessment. While the sensitivity and specificity for capturing tachycardia above a rate of 100 bpm were excellent (88% and 97%, respectively), the sensitivity of the remote monitoring system in capturing temperatures >37.8 °C and oxygen saturation <92% was 45% and 50%, respectively.ConclusionsOverall, this novel approach using temperature, heart rate, and oxygen saturation assessments successfully provided real-time, clinically valuable feedback to providers. While temperature and oxygen saturation assessments lagged in terms of sensitivity compared to a standard in-hospital system, the heart rate assessment provided highly accurate complementary data. As a whole, the system provided additional information that can be applied to a clinically vulnerable population. By transitioning its application to high-risk patients in the outpatient setting, this system can help prevent additional use of health care services through early provider intervention and potentially improve outcomes.